Narrow Results

Rhododendron arboreum Sm. (Burans) (family Ericaceae) has traditionally been used in Indian medicine to treat liver disorders. However, its mechanism against non-alcoholic fatty liver disease (NAFLD) remains elusive. This study utilized in silico methods – network pharmacology, ADMET prediction, molecular docking and molecular dynamics (MD) simulations for mechanistic exploration of Rhododendron arboreum leaves (RAL) in NAFLD. Bioactive compounds were sourced from open databases and assessed for drug-likeness and ADMET profiles. Network pharmacology identified key protein interactions using the STRING platform. GO analysis identified galactose metabolism, pentose and glucuronate interconversions and other processes in treating NAFLD. Molecular docking revealed that amyrin and pectolinarigenin had the highest binding affinities, with dock scores of –12.2 kcal/mol (AKR1C3-amyrin), –10.2 kcal/mol (PI3K-amyrin), –9.3 kcal/mol (AKR1C3-pectolinarigenin) and –9.6 kcal/mol (HSD17B1-pectolinarigenin). MD simulations, focusing on RMSD and RMSF analyses, confirmed the stability of these interactions. The RMSD graphs revealed stable binding pocket regions, highlighted in pink. Notably, the RMSF values for PHE (B:306) in the AKR1C3-amyrin complex and ARG (A:294) in the PI3K-amyrin interaction were 0.623 nm and 0.1586 nm, respectively, indicating stable ligand interactions. Our findings holistically clarify toxicity data, potential bioactives targets and molecular mechanisms of RAL against NAFLD, paving the way for future research.

β-Glucuronidase-inhibitory and hepatoprotective effects of Reduohanxiao-tang (Yuldahanso-tang), which has been used for liver diseases and stroke, on carbon tetrachloride (CCl₄)-induced hepatotoxicity of rats were investigated. Reduohanxiao-tang potently inhibited β-glucuronidases. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid dehydrogenase (LDH) levels of the CCl₄ group orally treated with Reduohanxiao-tang (100 mg/kg) were lowered to 54%, 71.5% and 66.1% of the CCl₄-treated control group, respectively. Among the ingredients of the Reduohanxiao-tang, the rhizomes of Pueraria thunbergiana and it Scutellaria baicalensis potently inhibited β-glucuronidases and protected against CCl₄-induced liver injury. Orally administered puerarin, which is a main component of Pueraria thunbergiana, showed potent hepatoprotective activity, but did not inhibit β-glucuronidase. However, daidzein, which is produced from puerarin by human intestinal bacteria, potently inhibited β-glucuronidase. These results suggest that β-glucuronidase inhibition by herbal medicines may protect a gainst CCl₄-induced liver injury.

It has been reported that Nigella sativa oil possesses hepatoprotective effects in some models of liver toxicity. However, it is N. sativa seeds that are used in the treatment of liver ailments in folk medicine rather than its oil. Therefore, the aim of this study was to investigate the effect of the aqueous suspension of N. sativa on carbon tetrachloride (CCL₄)-induced liver damage. Aqueous suspension of the seeds was given orally at two dose levels (250 mg/kg and 500 mg/kg) for five days. CCL₄ (250 μl/kg intraperitoneally/day in olive oil) was given to the experimental group on days 4 and 5, while the control group was only treated with the vehicles. Animals treated with CCL₄ showed remarkable centrilobular fatty changes and moderate inflammatory infiltrate in the form of neutrophil and mononuclear cells when compared to the controls. This effect was significantly decreased in animals pretreated with N. sativa. Histopathological or biochemical changes were not evident following administration of N. sativa alone. Serum levels of aspartic transaminase (AST), and L-alanine aminotransferase (ALT) were slightly decreased while lactate dehydrogenase (LDH) was significantly increased in animals treated with CCL₄ when compared to the control group. LDH was restored to normal but ALT and AST levels were increased in animals pretreated with N. sativa. In conclusion, N. sativa seeds appeared to be safe and possibly protective against CCL₄-induced hepatotoxicity. However, further studies may still be needed prior to supporting its use in folk medicine for hepatic diseases.

Chai-Hu-Ching-Kan-Tang (CHCKT) is one of the traditional Chinese medicine prescriptions commonly used to treat liver diseases. In this study, we evaluated the hepatoprotective effects of aqueous CHCKT extract at various concentrations (125, 250 and 500 mg/kg body weight) on acetaminophen (APAP)-induced acute liver injury in rats. Results showed that CHCKT treatments significantly decreased the level of serum glutamic oxaloacetic transaminase (sGOT) and glutamic pyruvic transaminase (sGPT) in APAP-treated groups. CHCKT also significantly decreased the level of lipid peroxides and increased the activity of antioxidant enzymes (i.e. SOD and GPx). Histopathological observation further confirmed the hepatoprotective activity of CHCKT as indicated by the amelioration in the central necrosis and fatty changes of the liver after APAP induction. Interestingly, the hepatoprotective activity of CHCKT at concentrations 125~500 mg/kg appeared to be as good as 12.5 mg/kg silymarin (a commercial hepatoprotective agent). Taken together, these results suggest that aqueous extract of CHCKT possesses potent hepatoprotective effects agianst APAP-induced liver injury in rats.

Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH^• radicals scavenging, Fe³⁺-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl₄-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.

The antioxidant activity and hepatoprotective potential of Cirsium setidens Nakai, a widely used medicinal plant, were investigated. The n-butanol (n-BuOH) fraction of leaves and roots of C. setidens had a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than the other soluble fractions. The n-BuOH fraction of roots of C. setidens had a significant hepatoprotective activity at a dose of 500 mg/kg compared to that of a standard agent. The biochemical results were confirmed by histological observations indicating that C. setidens extract decreased ballooning degeneration in response to CCl₄ treatment. The n-BuOH fraction reduced CCl₄-induced liver injury in rats, and transcript levels of genes encoding antioxidant enzymes such as glutathione peroxidase 1 (GPO1), glutathione peroxidase 3 (GPO3) and superoxide dismutase (SOD1) were elevated in the livers of rats treated with this fraction (500 mg/kg). Based on these results, we suggest that the C. setidens extract has hepatoprotective effect related to its antioxidant activity.

The hepatoprotective potential of Crossostephium chinensis (L.) Makino water extract (CCW) on carbon tetrachloride (CCl₄) induced liver damage was evaluated in preventive and curative rat models. Not only were indicators of hepatic damage including GPT, GOT, lipid peroxides and TBARS were examined, the activities of antioxidant enzymes (SOD, CAT, GPx) and GSH were examined as well. The results showed that CCW (0.1, 0.5 and 1.0 g/kg) significantly reduced the elevated levels of GPT and GOT by CCl₄ administration (p < 0.05). TBARS level was dramatically reduced, and SOD, CAT, GPx and GSH activities were significantly increased. In addition, CCW decreased NO production and TNF-α activation in CCl₄-treated rats. Therefore, we speculate that CCW protects against acute liver damage through its radical scavenging ability. CCW inhibited the expression of MMP-9 protein, indicating that MMP-9 played an important role in the development of CCl₄-induced chronic liver damage in rats. In LC-MS-MS analysis, the chromatograms of CCW with good hepatoprotective activities were established. Scopoletin may be an important bioactive compound in CCW.

The present study investigated the anti-oxidative and hepatoprotective effects of Glossogyne tenuifolia (GT) Cassini, against acetaminophen-induced acute liver injury in BALB/c mice. The extracts of GT by various solvents (hot water, 50% ethanol and 95% ethanol) were compared for their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing power, total phenolic content, and total anti-oxidant capacity. The results showed that hot water (HW) extracts of GT contained high levels of phenolics and exerted an excellent anti-oxidative capacity; thus, these were used in the animal experiment. The male BALB/c mice were randomly divided into control group, acetaminophen (APAP) group, positive control group and two GT groups at low (GT-L) and high (GT-H) dosages. The results showed that mice treated with GT had significantly decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). GT-H increased glutathione levels and the ratios of reduced glutathione and oxidized glutathione (GSH/GSSG) in the liver, and inhibited serum and lipid peroxidation. This experiment was the first to determine phenolic compounds, chlorogenic acid and luteolin-7-glucoside in HW extract of GT. In conclusion, HW extract of GT may have potential anti-oxidant capacity and show hepatoprotective capacities in APAP-induced liver damaged mice.